Homologous and Heterologous Boosting of the Chadox1-S1-S COVID-19 Vaccine With the SCB-2019 Vaccine Candidate: A Randomized, Controlled, Phase 2 Study
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Abstract
Background
Ongoing outbreaks of coronavirus disease 2019 (COVID-19) are driven by waning immunity following primary immunizations and emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that escape vaccine-induced neutralizing antibodies. It has been suggested that heterologous boosters could enhance and potentially maintain population immunity.
Methods
We assessed the immunogenicity and reactogenicity of booster doses of different formulations of aluminium hydroxide–adjuvanted SCB-2019 vaccine (9 μg of SCB-2019, with or without CpG-1018 adjuvant, or 30 μg of SCB-2019 with CpG-1018) in Brazilian adults primed with ChAdOx1-S vector vaccine. S-protein antibodies and ACE2-binding inhibition were measured by enzyme-linked immunosorbent assay (ELISA) on days 1, 15, and 29. Participants self-reported solicited adverse events and reactions.
Results
All SCB-2019 formulations increased S-protein ELISA antibodies and ACE2 binding inhibition to a greater extent than ChAdOx1-S. After 30 μg of SCB-2019 + CpG + aluminium hydroxide, titers against wild-type S-protein were significantly higher than after ChAdOx1-S on days 15 and 29, as were titers of neutralizing antibodies against the wild-type strain and Beta, Gamma, Delta, and Omicron variants. Boosting with SCB-2019 or ChAdOx1-S was well tolerated, with no vaccine-related serious or severe adverse events.
Conclusions
Boosting ChAdOx1-S-primed adults with SCB-2019 induced higher levels of antibodies against a wild-type strain and SARS-CoV-2 variants than a homologous ChAdOx1-S booster, with the highest responses being with the 30-μg SCB-2019 + CpG + aluminium hydroxide formulation.
Clinical Trials Registration
NCT05087368
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SciScore for 10.1101/2022.05.31.22275010: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: The study protocol was approved by each hospital’s Ethical Review committee and conducted according to the Declaration of Helsinki and Council for International Organizations of Medical Sciences International ethical guidelines and ICH GCP guidelines.
IACUC: The study protocol was approved by each hospital’s Ethical Review committee and conducted according to the Declaration of Helsinki and Council for International Organizations of Medical Sciences International ethical guidelines and ICH GCP guidelines.
Consent: Participants supplied written informed consent at enrolment.Sex as a biological variable Selection was to be based on the safety and immunogenicity, and potential impact on … SciScore for 10.1101/2022.05.31.22275010: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: The study protocol was approved by each hospital’s Ethical Review committee and conducted according to the Declaration of Helsinki and Council for International Organizations of Medical Sciences International ethical guidelines and ICH GCP guidelines.
IACUC: The study protocol was approved by each hospital’s Ethical Review committee and conducted according to the Declaration of Helsinki and Council for International Organizations of Medical Sciences International ethical guidelines and ICH GCP guidelines.
Consent: Participants supplied written informed consent at enrolment.Sex as a biological variable Selection was to be based on the safety and immunogenicity, and potential impact on supply of the chosen formulation, i.e. dose-sparing. Participants: Eligible participants were male or female adults, ≥ 18 years of age who had previously received two doses of ChAdOx1-S1-S vaccine 6 months (± 4 weeks) before enrolment and were willing and able to comply with study requirements, including all scheduled visits, vaccinations, laboratory tests, and other study procedures. Randomization This phase 2 randomized, controlled, observer-blinded, multi-center study is ongoing at three sites in Brazil: Hospital de Clínicas de Porto Alegre, Hospital Gloria D’or, Rio de Janeiro and Centro de Estudos e Pesquisa em Moléstias Infecciosas (CEPCLIN), Natal. Blinding not detected. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources The primary immunogenicity endpoint was ELISA antibody titers against SCB-2019 S-protein expressed as geometric mean titers (GMT), geometric mean-fold rise in titers over baseline (GMFR) and seroconversion rates (SCR) on Days 15 and 29 in all participants who received the correct vaccination and had no major protocol deviation reported or suffered a COVID-19 infection prior to blood draw. SCB-2019 S-proteinsuggested: NoneGMTs of neutralizing antibodies against prototype strain ELISA GMTs against SCB-2019 S-protein are presented in IU/mL, GMTs of neutralizing antibodies against variants and ACE2 are expressed in reciprocal units. ACE2suggested: NoneResults from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:This is a small study with several limitations as a consequence, but the trends are confirmation of other observations. Several studies have shown that heterologous booster vaccination can heighten and broaden the immune response compared with homologous booster doses [17–19]. We restricted this study to one priming vaccine, ChAdOx1-S, but results need to be confirmed with other vaccines, particularly mRNA and inactivated vaccines. We only assessed the immune responses out to four weeks after the booster vaccination, and persistence of any improved immune responses following the heterologous and homologous boosters will have to be assessed. Finally, we did not assess the efficacy of the booster immunization; although there were several cases of COVID-19 reported in this small study population it was not designed to include an efficacy assessment which would also require a placebo group. Notably, none of these cases were severe and there were no hospitalizations due to COVID-19. In conclusion, the formulation of 30 μg SCB-2019 adjuvanted with CpG-1018 and alum is safe and well tolerated and as a heterologous booster vaccine in those previously primed with ChAdOx1-S and is immunologically more effective than that same vaccine given as a homologous booster.
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT05087368 Not yet recruiting Immunogenicity and Safety of Heterologous and Homologous Boo… Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a protocol registration statement.
Results from scite Reference Check: We found no unreliable references.
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